6RHK

The crystal structure of human carbonic anhydrase II in complex with 4-(3-benzylimidazolidine-1-carbonyl)benzenesulfonamide

Summary for 6RHK

• Entry DOI: 10.2210/pdb6rhk/pdb
• Descriptor: Carbonic anhydrase 2, ZINC ION, 4-[3-(phenylmethyl)imidazolidin-1-yl]carbonylbenzenesulfonamide, ... (5 entities in total)
• Functional Keywords: lyase
• Biological source: Homo sapiens (Human)
• Total number of polymer chains: 1
• Total formula weight: 29884.08

Authors

Ferraroni, M.,Angeli, A.,Supuran, C.T. (deposition date: 2019-04-22, release date: 2020-05-13, Last modification date: 2024-01-24)

Primary citation

Chiaramonte, N.,Bua, S.,Angeli, A.,Ferraroni, M.,Picchioni, I.,Bartolucci, G.,Braconi, L.,Dei, S.,Teodori, E.,Supuran, C.T.,Romanelli, M.N.
Sulfonamides incorporating piperazine bioisosteres as potent human carbonic anhydrase I, II, IV and IX inhibitors.
Bioorg.Chem., 91:103130-103130, 2019

PubMed Abstract: Starting from the molecular simplification of (R) 4-(3,4-dibenzylpiperazine-1-carbonyl)benzenesulfonamide 9a, a compound endowed with selectivity for human Carbonic Anhydrase (hCA) IV, a series of piperazines and 4-aminopiperidines carrying a 4-sulfamoylbenzamide moiety as Zn-binding group have been designed and tested on human isoforms hCA I, II, IV and IX, using a stopped flow CO hydrase assay. The aim of the work was to derive structure-activity relationships useful for designing isoform selective compounds. These structural modifications changed the selectivity profile of the analogues from hCA IV to hCA I and II, and improved potency. Several of the new compounds showed subnanomolar activity on hCA II. X-ray crystallography of ligand-hCAII complexes was used to compare the binding modes of the new piperazines and the previously synthesized 2-benzyl-piperazine analogues, explaining the inhibition profiles.

PubMed: 31374520
DOI: 10.1016/j.bioorg.2019.103130

Experimental method

X-RAY DIFFRACTION (1.44 Å)